The proposed studies will investigate the pathobiologic significance of interactions of bacterial lipopolysaccharide (LPS) with in vivo "targets". These studies will focus on both the interactions of LPS with plasma as well as the interactions with tissue macrophages. The former studies will determine the mechanism by which the parent LPS is converted to a form with a hydrated buoyant density of less than 1.2 g/cm cubed by isolating the required plasma components. Studies with fixed macrophages, notably those present in the liver (Kupffer cells) will examine the effect of LPS on a number of macrophage factors which might participate in the initiation of LPS-induced injury. These studies will include measurement of changes in macrophage lysosomal enzymes, prostaglandins and procoagulant activity.